Separase prevents genomic instability by controlling replication fork speed

Proper chromosome segregation is crucial for preserving genomic integrity, and errors in this process cause chromosome mis-segregation, which may contribute to cancer development. Sister chromatid separation is triggered by Separase, an evolutionary conserved protease that cleaves the cohesin complex, allowing the dissolution of sister chromatid cohesion. Here we provide evidence that Separase participates in genomic stability maintenance by controlling replication fork speed. We found that Separase interacted with the replication licensing factors MCM2-7, and genome-wide data showed that Separase co-localized with MCM complex and cohesin. Unexpectedly, the depletion of Separase increased the fork velocity about 1.5-fold and caused a strong acetylation of cohesin's SMC3 subunit and altered checkpoint response. Notably, Separase silencing triggered genomic instability in both HeLa and human primary fibroblast cells. Our results show a novel mechanism for fork progression mediated by Separase and thus the basis for genomic instability associated with tumorigenesis

Separase prevents genomic instability by controlling replication fork speed

Proper chromosome segregation is crucial for preserving genomic integrity, and errors in this process cause chromosome mis-segregation, which may contribute to cancer development. Sister chromatid separation is triggered by Separase, an evolutionary conserved protease that cleaves the cohesin complex, allowing the dissolution of sister chromatid cohesion. Here we provide evidence that Separase participates in genomic stability maintenance by controlling replication fork speed. We found that Separase interacted with the replication licensing factors MCM2-7, and genome-wide data showed that Separase co-localized with MCM complex and cohesin. Unexpectedly, the depletion of Separase increased the fork velocity about 1.5-fold and caused a strong acetylation of cohesin's SMC3 subunit and altered checkpoint response. Notably, Separase silencing triggered genomic instability in both HeLa and human primary fibroblast cells. Our results show a novel mechanism for fork progression mediated by Separase and thus the basis for genomic instability associated with tumorigenesis

The accuracy of burn depth diagnosis: Clinical assessment before and after enzymatic debridement

Abstract Introduction The most common technique used to determine burn depth is clinical assessment by experienced burn surgeons, although this has been shown to be reliable in only 60–75% of the cases. Overestimation of burn depth may result in needles surgery, while burn depth underestimation can led to an increased length of stay in the hospital, risk of contracture and hypertrophic scar formation. The aim of this study was to assess the clinical evaluation of burn depth before and after enzymatic debridement with Nexobrid®. Methods The study model was retrospective. 69 patient records were collected at our burn units, from Jan 2018 to Jan 2019. Each target wound was directly assessed by a single expert physician before and after enzymatic debridement. It was investigated whether the expert, by single wound, would have indicated the need for skin grafts before treatment with Nexobrid® and after treatment. Results Prior to treatment with Nexobrid®, the expert physician assessed that a graft was necessary for 47/69 patients (68.1%). Following debridement, the same expert deemed that the patients needing a graft were 19/69 (27.5%); analysing K-agreement, a 40.6% discrepancy between the pre and post-treatment opinion with Nexobrid® was observed. Discussion The use of Nexobrid® enzymatic debridement can positively affect burn depth clinical assessment, increasing its specificity and sensitivity, without any need for delay. This can lead to a significant change in clinical practice, minimizing the use of surgery, therefore increasing quality and precision of the reconstructive phase

REM: Automatic for the People

We present the result of a year-long effort to think, design, build, realize, and manage the robotic, autonomous REM observatory, placed since June 2003 on the cerro La Silla, ESO Chile. The various aspects of the management and control are here surveyed, with the nice ideas and the wrong dead ends we encountered under way. Now REM is offered to the international astronomical community, a real, schedulable telescope, automatic for the People

the rem observing software

The Rapid Eye Mount (REM) is a 60 cm robotic telescope located at La Silla, Chile. Its Observing Software (REMOS) is constituted by a set of distributed intercommunicating processes organized around a central manager. Together they grant the system safety, automatically schedule and perform observations with two simultaneous cameras of user-defined targets, and drive fast reaction to satellite alerts. Subsequent data reduction is left to pipelines managed by each camera

Thyroid disease and autoimmunity in obese patients: a narrative review

Introduction: The high prevalence of obesity and thyroid diseases worldwide justifies di per se their simultaneous coexistence. In recent decades, there has been a parallel and significant rise in obesity and thyroid diseases in industrialised countries, although the underlying mechanisms are complex and not well known. Material and methods: The authors accomplished a comprehensive literature search of original articles concerning obesity and thyroid status. Original papers exploring the association between these two morbidities in children and adults were included. Results: A total of 79 articles were included in the present analysis. A total of 12% of obese children (mean age 10.9 ± 1.4 years) showed a thyroid disease, and they were younger than healthy obese children (10.9 ± 1.2 vs. 11.0 ± 0.4 years, p < 0.001). Isolated hyperthyrotropinaemia was the most frequent finding in children (10.1%). Autoimmune thyroid disease was more frequent in puberal age. Thyroid antibodies and subclinical hypothyroidism were more frequent in obese that in non-obese patients (7% vs. 3%, p < 0.001; 10% vs. 6%, p < 0.001). Among obese adults, 62.2% displayed a thyroid disease; those affected were younger (35.3 ± 6.8 vs. 41.0 ± 1.9 years, p < 0.001), heavier [body mass index (BMI): 39.4 ± 6.3 vs. 36.1 ± 2.3 kg/m2, p < 0.001], and more frequently female (13% vs. 8%, p < 0.001). The most frequent disease was overt hypothyroidism (29.9%). BMI appears to be correlated with TSH levels in obese adults. Overt hypothyroidism was significantly more frequent in obese patients (7% vs. 3%, p < 0.005), but no difference was found in thyroid antibodies (15% vs. 14%, p = 0.178). Conclusions: An undeniable relationship between obesity and thyroid impairments exists. Isolated hyperthyrotropinaemia is frequently seen in obese children, often followed by spontaneous resolution. Subclinical hypothyroidism should never be treated in children or adults with the aim of reducing body weight

Outward Migration of Jupiter and Saturn in Evolved Gaseous Disks

The outward migration of a pair of resonant-orbit planets, driven by tidal interactions with a gas-dominated disk, is studied in the context of evolved solar nebula models. The planets' masses, M1 and M2, correspond to those of Jupiter and Saturn. Hydrodynamical calculations in two and three dimensions are used to quantify the migration rates and analyze the conditions under which the outward migration mechanism may operate. The planets are taken to be fully formed after 1e6 and before 3e6 years. The orbital evolution of the planets in an evolving disk is then calculated until the disk's gas is completely dissipated. Orbital locking in the 3:2 mean motion resonance may lead to outward migration under appropriate conditions of disk viscosity and temperature. However, resonance locking does not necessarily result in outward migration. This is the case, for example, if convergent migration leads to locking in the 2:1 mean motion resonance, as post-formation disk conditions seem to suggest. Accretion of gas on the planets may deactivate the outward migration mechanism by raising the mass ratio M2/M1 and/or by reducing the accretion rate toward the star, hence depleting the inner disk. For migrating planets locked in the 3:2 mean motion resonance, there are stalling radii that depend on disk viscosity and on stellar irradiation, when it determines the disk's thermal balance. Planets locked in the 3:2 orbital resonance that start moving outward from within 1-2 AU may reach beyond 5 AU only under favorable conditions. However, within the explored space of disk parameters, only a small fraction - less than a few per cent - of the models predict that the interior planet reaches beyond 4 AU.Comment: 24 pages, 22 figures. To appear in The Astrophysical Journal. Updated with corrections added in proo

imaging of renal angiomyolipomatosis

Angiomyolipoma is a type of benign renal tumor. It is sporadic and isolated in 80% of cases. The remaining 20% is associated with tuberous sclerosis complex or pulmonary lymphangioleiomyomatosis. Generally, angiomyolipomas manifest themselves as angiomyolipomatosis, in which the angiomyolipomas are larger, bilateral, and widespread. Understanding whether angiomyolipomas are present in the context of angiomyolipomatosis is of considerable importance because it might be associated with malignant lesions. This article provides an overview of the radiological features of renal angiomyolipomatosis under different imaging techniques such as ultrasound, computed tomography, and magnetic resonance

Resolved Images of Large Cavities in Protoplanetary Transition Disks

Circumstellar disks are thought to experience a rapid "transition" phase in their evolution that can have a considerable impact on the formation and early development of planetary systems. We present new and archival high angular resolution (0.3" = 40-75 AU) Submillimeter Array (SMA) observations of the 880 micron dust continuum emission from 12 such transition disks in nearby star-forming regions. In each case, we directly resolve a dust-depleted disk cavity around the central star. Using radiative transfer calculations, we interpret these dust disk structures in a homogeneous, parametric model framework by reproducing their SMA visibilities and SEDs. The cavities in these disks are large (R_cav = 15-73 AU) and substantially depleted of small (~um-sized) dust grains, although their mass contents are still uncertain. The structures of the remnant material at larger radii are comparable to normal disks. We demonstrate that these large cavities are common among the millimeter-bright disk population, comprising at least 20% of the disks in the bright half of the millimeter luminosity (disk mass) distribution. Utilizing these results, we assess some of the physical mechanisms proposed to account for transition disk structures. As has been shown before, photoevaporation models do not produce the large cavity sizes, accretion rates, and disk masses representative of this sample. It would be difficult to achieve a sufficient decrease of the dust optical depths in these cavities by particle growth alone: substantial growth (to meter sizes or beyond) must occur in large (tens of AU) regions of low turbulence without also producing an abundance of small particles. Given those challenges, we suggest instead that the observations are most commensurate with dynamical clearing due to tidal interactions with low-mass companions --young brown dwarfs or giant planets on long-period orbits.Comment: ApJ, in pres